A basic problem in the construction of medical devices having components that must contact blood and other physiological fluids is that materials with good mechanical and structural properties have rather poor biocompatibility, while highly biocompatible materials have poor structural properties. Biocompatibility is itself a multi-faceted problem which has different aspects depending on the type of device, what tissues or fluids it contacts, and the length of contact time. In devices designed for hemodialysis or blood oxygenation, the materials are in contact with blood flowing through tubing, into containers, through heat exchangers and over membranes. The blood returns to the patient's body. The primary elements of biocompatibility are therefore to prevent initiating processes which can subsequently injure the patient, such as activation of clotting mechanisms, activation of the complement system, and initiation of inflammatory reactions. Materials must not be soluble in blood or other body fluids to avoid being carried permanently into the patient's body.
Although certain types of polymers, such as silicones and siloxanes, are known to possess many attributes of biocompatibility, there are no reliable physical correlates which enable one to predict biocompatibility with any degree of certainty. Generally, hydrophobic surfaces are more biocompatible than hydrophilic surfaces. Zisman's critical surface tension [Zisman, W. A. (1964) Adv. Chem. Ser. 43] has been used as a parameter to help assess potential biocompatibility. Materials with an optimum critical surface tension are frequently biocompatible, yet there are notable exceptions. For example, polyethylene and polypropylene have critical surface tensions well within the optimum range, but they are not predictably biocompatible. Other factors are also important. Without a clear understanding of the nature of these factors, biocompatibility remains unpredictable.
Because of the attractive structural properties of polyolefins and polyurethanes, various blending and co-polymerization techniques have been developed to impart greater biocompatibility. U.S. Pat. 4,872,867 discloses modifying a polyurethane with a water soluble polymer and crosslinking them in situ with a silane-type coupling-agent to form a cross-linked and intertwined polysiloxane network. U.S. Pat. 4,636,552 discloses a polydimethyl siloxane with polylactone side chains which are said to be useful for imparting biocompatibility when combined with a base polymer, or used to replace plasticizer. U.S. Pat. 4,929,510 discloses a diblock copolymer having a more hydrophobic block and a less hydrophobic block. A solution of the diblock copolymer in a solvent which swells the matrix polymer is used to introduce the diblock into an article of matrix polymer. Thereafter, the article is transferred to water, to force orientation of the incorporated diblock copolymer such that the more hydrophobic block is embedded in the matrix and the less hydrophobic block is exposed on the surface of the article. Examples of diblock copolymers included poly (ethyleneoxide-propylene oxide), N-vinyl-pyrrolidone-vinyl acetate and N-vinyl-pyrrolidone-styrene. U.S. Pat. Nos. 4,663,413 and 4,675,361 disclose segmented block copolymers, in particular polysiloxane-polycaprolactone linear block copolymers. The latter were incorporated into base polymer materials to modify the surface properties thereof. Although initially blended in bulk into the base polymer, the copolymer migrates to the surface to form an exceptionally thin, possibly a monolayer film which imparts the desired surface characteristic, specifically, biocompatibility.
Although numerous surface-modifying compositions have been disclosed in the art, their intended use has been as bulk formulation additives, as mixtures with base polymer, cross-linked within the polymer matrix, as substitutes for plasticizer or incorporated into the polymer matrix. The art has avoided coatings, in part because of increased manufacturing cost and difficulty of uniform application. For certain applications such as microporous membranes, application of a coating could adversely affect membrane properties by plugging membrane pores or otherwise degrading performance. In the case of microporous membranes made by a process of stretching polymer film stock, total surface area is expanded to the extent that the available surface concentration of surface modifiers added in conventional formulation processes is reduced to ineffectiveness. Providing a biocompatible surface for a microporous membrane remains a matter of critical importance, since the membrane has the largest surface area in contact with a patient's blood of any component of an oxygenator or hemodialysis unit. Another component with a large blood contact area is a heat exchanger, commonly fabricated of metal, used to maintain a desired extracorporeal blood temperature. Aluminum, titanium and stainless steel are all used for various sorts of blood-contacting devices. Aluminum is reactive with blood and is commonly coated with epoxy or polyurethane to prevent adverse reactions. Although less reactive than aluminum, both stainless steel and titanium have sub-optimal biocompatibility in contact with blood.
From what is known of their properties as bulk additives, the triblock copolymers would be unlikely candidates for use as coatings since the blocks that normally anchor the copolymer within the base polymer matrix would be exposed on the surface. Nevertheless, as detailed herein, it has now been found that certain triblock copolymers can be applied as coatings to impart biocompatibility to polymeric surfaces. It has also been found unexpectedly that the same copolymers can be used to coat surfaces of other polymeric and metallic articles, imparting excellent biocompatibility to them. The same copolymers also improve the biocompatibility of polymer-coated metal surfaces, for example, aluminum coated with epoxy or polyurethane.